Canadian Cancer Trials Group - Tumour Bank
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CO29 Details
Status: Closed 
Activation Date: 2021FEB09
Closing Date: 2023MAR31
Phase: II-III 

Description: Circulating Tumor DNA Analysis Informing Adjuvant Chemotherapy in Stage III Colon Cancer: A Multicentre Phase II/III Randomised Controlled Study (DYNAMIC III) 

Eligibility: - Patients aged >=18 years of age - Subjects with curatively resected stage III (Any T, N1 or N2, M0) colorectal cancer - Patients with rectal cancer will be eligible unless they have had pre-operative combined chemotherapy and radiotherapy, or are scheduled for post-operative combined chemotherapy and radiotherapy. All rectal cancer patients must have had TME type surgery with negative (R0) resection margins. - A representative tumour sample is available for molecular testing up to 6 weeks after surgery (refer to section 9.1.1 for a more specific timeframe) - Fit for at least single agent fluoropyrimidine adjuvant chemotherapy - ECOG performance status 0-2 - No metastatic disease  

Objective: Primary objective: To evaluate the impact of a de-escalation/escalation treatment strategy using ctDNA-informed management. The ctDNA positive and negative cohorts will be evaluated separately: (a) For ctDNA negative patients: de-escalation treatment strategy is non-inferior to standard of care (b) For the ctDNA positive patients: escalation treatment strategy is superior to standard of care. Secondary objectives: To demonstrate (1) ctDNA-informed adjuvant therapy approach will not compromise RFS in patients with NEGATIVE post-op ctDNA; (2) an acceptable rate of de-escalation in the ctDNA-informed negative cohort; (3) 3-year RFS rates between ctDNA-informed therapy and standard of care in patients with POSITIVE post-op ctDNA; (4) OS between ctDNA-informed therapy and standard of care in patients with POS & NEG post-op ctDNA; (5) end of treatment ctDNA results with RFS and OS; (6) feasibility of adjuvant chemo strategy based on post-op ctDNA results; (7) Heath economic impact 

Participation: Open to member centres 

Lay Description: Colorectal cancer is the second most common cause of cancer death in Canada. These cancers start in the colon or rectum and can spread, or become metastatic, at which point most colorectal cancers are not curable. One of the first places these cancers spread is regional lymph nodes that serve as filters in the body and house the immune system to fight infections and cancers. During a colon cancer surgery, the lymph nodes near a tumor are removed, however in patients where lymph nodes have cancer found in them (termed stage III), the risk of the cancer coming back somewhere in the body is around 50%. By giving chemotherapy after surgery (termed adjuvant chemotherapy), we can reduce these risks. Clinicians use the number of lymph nodes affected by a cancer as well as the depth of cancer penetration into the bowel wall to predict the risk of a cancer recurring and help personalize the type of chemotherapy given and the duration of this adjuvant chemotherapy. The problem is that many patients who receive adjuvant chemotherapy were cured before the chemotherapy and undergo undue toxicity, while others undergo adjuvant treatment but still have their cancer come back. Tools are needed to better risk stratify patients and personalize adjuvant therapy decisions. Recently it has become possible to detect the mutations from a cancer in the blood of patients. Measuring this circulating tumor DNA (ctDNA) provides information about the mutations of a cancer as well as the risk of a cancer returning. ctDNA only stays in the blood for a short time and it has been shown that the presence of ctDNA from a cancer after surgery is highly predictive of a cancer still being present. In a recent Australian study, they demonstrated that the risk for patients with stage II colon cancer who had detectable ctDNA after surgery was 18 times higher than if it was negative. Using this information, the DYNAMIC III trial was designed to test whether the presence or absence of ctDNA can be used to personalize adjuvant therapy with two main goals. For patients with negative ctDNA, treatment will be de-escalated and the safety and efficacy of this will be compared to the standard chemotherapy that these patients would have received. For patients with positive ctDNA, treatment will be escalated to see if we can improve the outcomes for this extremely high risk group, almost all of whom are expected to relapse without 

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Disease Site Trial Code Patients Accrued Patients - Blocks Patients - Slides Patients - Blocks and/or Slides
GASTRO-INTESTINAL CO29 223 164 9 168
Hide TMA Samples
(Core size is 0.6 mm)
Disease Site Trial Code Patients Accrued TMA Blocks Patients on TMA Blocks
GASTRO-INTESTINAL CO29 223 0 0
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Disease Site Trial Code Patients Accrued Patients - Whole Blood Patients - Cellular Component of Blood Patients - DNA extracted from Blood Patients - RNA extracted from Blood Patients - Plasma Patients - Serum Patients - Urine Patients - Buccal
GASTRO-INTESTINAL CO29 223 217 0 0 0 169 0 0 0